Summary of Study ST002316

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001484. The data can be accessed directly via it's Project DOI: 10.21228/M8WT54 This work is supported by NIH grant, U2C- DK119886.

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This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST002316
Study TitleDifferential requirements for mitochondrial electron transport chain components in the adult murine liver - Untargeted Metabolomics (qTOF)
Study SummaryWild-type and knockout mice (Ndufa9 and Cox10) livers were harvested on liquid nitrogen. Samples were crushed on liquid nitrogen, lysed in 80% ACN, and immediately injected onto the QE.
Institute
The University of Texas Southwestern Medical Center at Dallas
DepartmentChildren's Research Institute
LaboratoryPrashant Mishra
Last NameLesner
First NameNicholas
Address6000 Harry Hines BLVD
Emailnicholas.lesner@pennmedicine.upenn.edu
Phone2146483784
Submit Date2022-08-23
Num Groups8
Total Subjects60
Raw Data AvailableYes
Raw Data File Type(s)mzXML
Analysis Type DetailLC-MS
Release Date2022-11-01
Release Version1
Nicholas Lesner Nicholas Lesner
https://dx.doi.org/10.21228/M8WT54
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:

Project:

Project ID:PR001484
Project DOI:doi: 10.21228/M8WT54
Project Title:Differential requirements for mitochondrial electron transport chain components in the adult murine liver
Project Summary:Mitochondrial electron transport chain (ETC) dysfunction due to mutations in the nuclear or mitochondrial genome is a common cause of metabolic disease in humans, and displays striking tissue specificity depending on the affected gene. The mechanisms underlying tissue specific phenotypes are not understood. Complex I (cI) is classically considered the entry point for electrons into the ETC, and in vitro experiments indicate that cI is required for basal respiration and maintenance of the NAD+/NADH ratio, an indicator of cellular redox status. This finding has largely not been tested in vivo. Here, we report that mitochondrial complex I (cI) is dispensable for homeostasis of the adult mouse liver; animals with hepatocyte-specific loss of cI function display no overt phenotypes or signs of liver damage, and maintain liver function, redox and oxygen status. Further analysis of cI-deficient livers did not reveal significant proteomic or metabolic changes, indicating little to no compensation is required in the setting of complex I loss. In contrast, complex IV (cIV) dysfunction in adult hepatocytes results in decreased liver function, impaired oxygen handling, steatosis, and liver damage, accompanied by significant metabolomic and proteomic perturbations. Metabolomic analysis suggests that the electron transfer flavoprotein complex constitutes a major route for electron entry into the hepatic ETC. Our results support a model whereby complex I loss is tolerated in the mouse liver because hepatocytes use alternative electron donors to fuel the mitochondrial ETC.
Institute:The University of Texas Southwestern Medical Center at Dallas
Department:Children's Research Institute
Laboratory:Prashant Mishra
Last Name:Lesner
First Name:Nicholas
Address:6000 Harry Hines BLVD
Email:nicholas.lesner@pennmedicine.upenn.edu
Phone:2146483784

Subject:

Subject ID:SU002402
Subject Type:Mammal
Subject Species:Mus musculus
Taxonomy ID:10090

Factors:

Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)

mb_sample_id local_sample_id Genotype
SA22722611cox10-/-
SA22722710cox10-/-
SA2272289cox10-/-
SA2272296cox10-/-
SA2272307cox10-/-
SA2272318cox10-/-
SA2272211Cox10f/f
SA2272225Cox10f/f
SA2272234Cox10f/f
SA2272242Cox10f/f
SA2272253Cox10f/f
SA22723220ndufa9-/-
SA22723318ndufa9-/-
SA22723421ndufa9-/-
SA22723523ndufa9-/-
SA22723619ndufa9-/-
SA22723722ndufa9-/-
SA22723812ndufa9f/f
SA22723913ndufa9f/f
SA22724014ndufa9f/f
SA22724115ndufa9f/f
SA22724216ndufa9f/f
SA22724317ndufa9f/f
Showing results 1 to 23 of 23

Collection:

Collection ID:CO002395
Collection Summary:Liver was frozen on liqN2. Liver was crushed on liqN2, and metabolites extracted with 80% meOH. MeOH was dried, and samples resuspended in MPA and injected onto a qTOF.
Sample Type:Liver

Treatment:

Treatment ID:TR002414
Treatment Summary:8 weeks post AAV injection the mouse liver was pulverized, metabolites extracted

Sample Preparation:

Sampleprep ID:SP002408
Sampleprep Summary:80% methanol containing metabolites was dried overnight in a speedvac. Dried pellets were derivatized using methoxyamine and MTBSTFA. Samples were immediately injected.

Combined analysis:

Analysis ID AN003783
Analysis type MS
Chromatography type Reversed phase
Chromatography system Agilent 1290
Column Waters Acquity UPLC HSS T3 (150 x 2.1mm,1.8um)
MS Type ESI
MS instrument type QTOF
MS instrument name Agilent 6550 QTOF
Ion Mode UNSPECIFIED
Units area

Chromatography:

Chromatography ID:CH002797
Chromatography Summary:Data acquisition was performed by reverse-phase chromatography on a 1290 UHPLC liquid chromatography (LC) system interfaced to a high-resolution mass spectrometry (HRMS) 6550 iFunnel Q-TOF mass spectrometer (MS) (Agilent Technologies, CA). The MS was operated in both positive and negative (ESI+ and ESI-) modes. Analytes were separated on an Acquity UPLC® HSS T3 column (1.8 μm, 2.1 x 150 mm, Waters, MA). The column was kept at room temperature. Mobile phase A composition was 0.1% formic acid in water and mobile phase B composition was 0.1% formic acid in 100% ACN. The LC gradient was 0 min: 1% B; 5 min: 5% B; 15 min: 99% B; 23 min: 99% B; 24 min: 1% B; 25 min: 1% B. The flow rate was 250 μL min-1. The sample injection volume was 5 μL. ESI source conditions were set as follows: dry gas temperature 225 °C and flow 18 L min-1, fragmentor voltage 175 V, sheath gas temperature 350 °C and flow 12 L min-1, nozzle voltage 500 V, and capillary voltage +3500 V in positive mode and −3500 V in negative. The instrument was set to acquire over the full m/z range of 40–1700 in both modes, with the MS acquisition rate of 1 spectrum s-1 in profile format. Raw data files were processed using Profinder B.08.00 SP3 software (Agilent Technologies, CA) with an in-house database containing retention time and accurate mass information on 600 standards from Mass Spectrometry Metabolite Library (IROA Technologies, MA) which was created under the same analysis conditions. The in-house database matching parameters were mass tolerance 10 ppm; retention time tolerance 0.5 min. Peak integration result was manually curated in Profinder for improved consistency
Chromatography Comments:The LC gradient was 0 min: 1% B; 5 min: 5% B; 15 min: 99% B; 23 min: 99% B; 24 min: 1% B; 25 min: 1% B.
Instrument Name:Agilent 1290
Column Name:Waters Acquity UPLC HSS T3 (150 x 2.1mm,1.8um)
Flow Gradient:0 min: 1% B; 5 min: 5% B; 15 min: 99% B; 23 min: 99% B; 24 min: 1% B; 25 min: 1% B
Flow Rate:250 uL/min
Injection Temperature:37
Sample Injection:5 uL
Solvent A:100% water; 0.1% formic acid
Solvent B:100% acetonitrile; 0.1% formic acid
Chromatography Type:Reversed phase

MS:

MS ID:MS003526
Analysis ID:AN003783
Instrument Name:Agilent 6550 QTOF
Instrument Type:QTOF
MS Type:ESI
MS Comments:The MS was operated in both positive and negative (ESI+ and ESI-) modes. Raw data files were processed using Profinder B.08.00 SP3 software (Agilent Technologies, CA) with an in-house database containing retention time and accurate mass information on 600 standards from Mass Spectrometry Metabolite Library (IROA Technologies, MA) which was created under the same analysis conditions. The in-house database matching parameters were mass tolerance 10 ppm; retention time tolerance 0.5 min. Peak integration result was manually curated in Profinder for improved consistency
Ion Mode:UNSPECIFIED
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